Meat Consumption and Cancer Research Paper

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Introduction

Much of the global variation in cancer incidence has been attributed to environmental factors, such as diet. Thus far, one of the constituents of diet that has been most consistently associated with elevated risks of certain cancers is meat, particularly consumption of red and processed meats. Meat intake varies enormously throughout the globe, with some populations consuming relatively little meat, while in some countries, such as Argentina and Australia, meat provides a large percentage of daily caloric intake.

There have been several reviews of the meat and cancer association, including two large consensus reports from the World Cancer Research Fund (1997) and the Committee on Medical Aspects of Food and Nutrition Policy (1998). The recommendation from these reports was to prevent the average level of red meat and processed meat consumption from rising; people consuming high levels (>140 g/day) were advised to reduce their intake. The WCRF report concluded that an association between meat and colorectal cancer was ‘probable.’ In addition, this report concluded that there was a ‘possible’ association between meat and cancers of the pancreas, prostate, breast, and kidney (World Cancer Research Fund, 1997). The WCRF report is being updated; although the publication has not yet been released, it is likely that the recommendation to limit meat consumption will be strengthened.

Epidemiology

The amount of epidemiologic evidence on meat intake and cancer risk varies depending on the anatomic site. All of the studies with cancer as an endpoint have been observational cohort and case-control studies rather than clinical trials, although there have been some controlled feeding studies, which is discussed below. This section summarizes the epidemiologic literature for the cancer sites most commonly thought to have risks modifiable by dietary components. The most stable risk estimates are obtained from meta-analyses or pooled analyses, rather than individual studies.

Colorectal Cancer

The relationship between meat consumption and cancer of the colorectum has been studied more extensively than that with other cancer sites. In 2001, a meta-analysis pooled results from 13 prospective studies and concluded that an increase of 100 g/day of all meat or red meat was associated with a statistically significant 12–17% increased risk of colorectal cancer, and an increase of 25 g/day of processed meat was associated with a 49% increased risk (Sandhu et al., 2001). The following year, results from 34 case-control studies and 14 cohort studies of meat intake and colorectal cancer were reviewed, of which 15 case-control studies and nine cohort studies examined red meat intake specifically and 22 case-control and seven cohort studies examined processed meat specifically (Norat et al., 2002). This review found a statistically significant increased risk for colorectal cancer for those in the highest quantile of red meat (RR = 1.35; 95% CI = 1.21–1.51) and processed meat (RR = 1.31; 95% CI= 1.13–1.5) (Norat et al., 2002). More recently, a meta-analysis of the prospective studies through March 2006, which included 19 studies, confirmed the positive association in the summary statistics for both red meat (RR = 1.28; 95% CI = 1.15–1.42) and processed meat (RR = 1.20; 95% CI = 1.11–1.31) in the highest versus lowest categories of intake (Larsson and Wolk, 2006).

In contrast, some researchers have questioned the role of meat in colorectal cancer etiology. A pooled analysis of five cohort studies, each with a high proportion of vegetarians, showed no difference in the risk of mortality from colorectal cancer in vegetarians compared with meateaters (Key et al., 1999). However, this study had a high proportion of vegetarians and very few heavy meat-eaters; furthermore, the definition of regular meat-eaters was those who consumed meat just once per week or more.

Esophageal And Gastric Cancer

There is very little known about meat as a risk factor for esophageal cancer. The first cohort study to investigate this association in a Western population was published in 2006 (Gonzalez et al., 2006); this study examined adenocarcinoma of the esophagus and found no association for meat intake overall, but it did report increased risk for those in the highest tertile of processed meat consumption.

With regard to gastric cancer, total meat intake was not associated with risk in three cohorts (Ito et al., 2003; Kneller et al., 1991; Ngoan et al., 2002). Red meat intake was also not associated with gastric cancer risk in two large case-control studies (Boeing et al., 1991; Ji et al., 1998), but was associated with an elevated risk in several other case-control studies (Chen et al., 2002; Correa et al., 1985; Mathew et al., 2000; Ward et al., 1999; Zhang et al., 1997), although only two reached statistical significance (Correa et al., 1985; Ward et al., 1999). Processed meat consumption has also been associated with risk of gastric cancer in several case-control (Boeing et al., 1991; Correa et al., 1985; Ward et al., 1999; Buiatti et al., 1989; Gonzalez et al., 1991; Hoshiyama and Sasaba, 1992; Risch et al., 1985; Ward et al., 1997) and cohort studies (Kneller et al., 1991; Ngoan et al., 2002; Chyou et al., 1990; Nomura et al., 1990; van den Brendt et al., 2003), but not in others (Ito et al., 2003; Galanis et al., 1998; McCullough et al., 2001). None of the studies mentioned above looked separately at cancers of the gastric cardia and non-cardia, the two main subtypes of gastric cancer. Recently, a large, multicentered cohort within Europe published findings for gastric cancer by sub-site; the authors found significantly elevated risks for non-cardia cancer for total meat (3.5-fold risk), red meat (1.7-fold risk), as well as processed meat (2.5-fold risk), but no associations with gastric cardia cancer (Gonzalez et al., 2006).

Pancreatic Cancer

Meat intake as a risk factor for pancreatic cancer has been investigated in many case-control studies (Bueno de Mesquita et al., 1991; Falk et al., 1988; Farrow and Davis, 1990; Fernandez et al., 1996; La Vecchia et al., 1990; Lyon et al., 1993; Mizuno et al., 1999; Olsen et al., 1989; Raymond et al., 1987; Silverman et al., 1998; Soler et al., 1998; Anderson et al., 2002; Baghurst et al., 1991; Ghadirian et al., 1995; Gold et al., 1985; Ji et al., 1995; Mack et al., 1986; Norell et al., 1986; Tavani et al., 2000), as well as several cohort studies (Coughlin et al., 2000; Hirayama, 1989; Isaksson et al., 2002; Larsson et al., 2000; Mills et al., 1988; Zheng et al., 1993; Michaud et al., 2003; Nothlings et al., 2005; Stolzenberg-Solomon et al., 2002), with mixed results. The majority of studies reported either positive (Falk et al., 1988; Farrow and Davis, 1990; Lyon et al., 1993; Olsen et al., 1989; Soler et al., 1998; Anderson et al., 2002; Ghadirian et al., 1995; Mack et al., 1986; Norell et al., 1986; Tavani et al., 2000; Hirayama, 1989; Larsson et al., 2006; Mills et al., 1988; Zheng et al., 1993; Nothlings et al., 2005) or null results (Bueno de Mesquita et al., 1991; Falk et al., 1988; Fernandez et al., 1996; La Vecchia et al., 1990; Mizuno et al., 1992; Olsen et al., 1989; Raymond et al., 1987; Silverman et al., 1998; Baghurst et al., 1991; Ji et al., 1995; Coughlin et al., 2000; Michaud et al., 2003; Stolzenberg-Solomon, 2002), although few have reported inverse associations (Bueno di Mesquita et al., 1991; Silverman et al., 1998; Gold et al., 1985; Isaksson et al., 2002).

Prostate Cancer

The findings regarding meat intake and prostate cancer are inconsistent, with some studies reporting no relationship (Bosetti et al., 2004; Cross et al., 2005; Gronberg et al., 1996; Hayes et al., 1999; Hirayama, 1979; Hsing et al., 1990; Whittemore et al., 1995) and others reporting positive associations (Deneo-Pellegrini et al., 1999; Gann et al., 1994; Giovannucci et al., 1993; Le Marchand et al., 1994; Michaud et al., 2001; Schuurman et al., 1999; Veierod et al., 1997; Villeneuve, 1999). Most recently, a large U.S. cohort that examined the association between meat and prostate cancer risk separately in whites and African-Americans found no association in white men, but significantly elevated risks in black men. The relative risk estimates comparing the top to the bottom quartile were 2.0 for red meat, 2.4 for processed meat, and 2.7 for cooked processed meat (2.7-fold risk) (Rodriguez et al., 2006). A racial difference in the association between meat and prostate cancer has been observed previously (Hayes et al., 1999).

Breast Cancer

The evidence for meat intake as a risk factor for breast cancer is also inconsistent. There have been two reviews of the evidence, one meta-analysis of published literature from 22 case-control and nine cohort studies through July, 2003 (Boyd et al., 2003), and one pooled analysis of eight prospective studies (Missmer et al., 2002). The meta-analysis found an overall positive association for meat intake and breast cancer risk (RR = 1.17; 95% CI = 1.06–1.29), with a stronger association for the cohort studies (RR = 1.32; 95% CI = 1.12–1.56) (Boyd et al., 2003). However, the pooled analysis found no association between total meat or red meat intake and breast cancer risk (Missmer et al., 2002). The two most recent prospective studies found elevated risks for breast cancer with high intake of both red and processed meats (Taylor et al., 2007), specifically for estrogen and progesterone-receptorpositive pre-menopausal breast cancer (RR = 1.97; 95% CI = 1.35–2.88) (Cho et al., 2006).

Non-Hodgkin Lymphoma

The incidence rates for non-Hodgkin lymphoma (NHL) have increased since the mid-1970s, yet there are few established risk factors. Dietary risk factors have not been extensively investigated, with the majority of studies suggesting a positive association for fat and protein intake, which led to a few studies that examined meat intake. One cohort study (Chiu et al., 1996) and one large case-control study (Purdue et al., 2004) reported elevated risks for total meat intake and NHL risk, although three other casecontrol studies reported null associations (Cross et al., 2006; Tavani et al., 2007; Ward et al., 1994). The results have been inconsistent with respect to red meat; most studies have not found an association for NHL (Tavani et al., 2000; Purdue et al., 2004; Cross et al., 2006; Ward et al., 1994; Chang et al., 2005; Franceschi et al., 1989; Talamani et al., 2006; Zheng et al., 2004), although two female cohorts (Chiu et al., 1996; Zhang et al., 1999) and one case-control study in men (De Stefani et al., 1998) found twoto 2.5-fold elevated risks. Of nine studies (Chiu et al., 1996; Purdue et al., 2004; Cross et al., 2006; Tavani et al., 1997; Ward et al., 1994; Franceschi et al., 1989; Talamani et al., 2006; Zhang et al., 1999; De Stefani et al., 1998) investigating processed meat as a risk factor for NHL, only two found an elevated risk (Purdue et al., 2004; Tavani et al., 1997).

Bladder Cancer

There have been few studies of meat intake in relation to bladder cancer. Two cohort studies have reported elevated, but not statistically significant, risks of bladder cancer for those in the highest category of meat consumption (Chyou et al., 1993; Mills et al., 1991), although other studies have reported null findings (La Vecchia and Negri, 1996; Steinmaus et al., 2000). With regard to red meat specifically, one cohort study found a 2.2-fold increased risk for bladder cancer (Steineck et al., 1988), whereas another found no association (Michaud et al., 2006). Processed meat intake has been associated with bladder cancer risk in one case-control study (Wilkens et al., 1996) and two prospective cohorts combined found a 1.6-fold increased risk for bacon intake (Michaud et al., 2006), whereas another cohort did not (Chyou et al., 1993).

Mechanisms

There are several plausible biological mechanisms to explain an association between meat consumption and cancer. Early hypotheses focused on the potential effects of saturated fat or protein in red meat on colon cancer. Subsequent research has implicated other components of meat that could contribute to carcinogenesis such as iron in red meat, mutagens associated with meat preparation, and substances used to preserve meat, as noted below.

Preservation And Processing

Curing meat by adding salt, nitrate, or nitrite or by smoking has been a method of preservation for years. Most of the research regarding meat preservation methods has focused on cancers of the gastrointestinal tract; these studies were summarized by the WCRF report, which concluded that there was ‘possible’ evidence for an association between cured meats and colorectal cancer (World Cancer Research Fund, 1997). Other cancers that have been associated with processed meat consumption include childhood leukemia (Peters et al., 1994) and cancer of the brain (Preston-Martin et al., 1982; Sarasua and Savitz, 1994), oral cavity (Rajkumar et al., 2003), larynx (Levi et al., 2004), prostate (Michaud et al., 2001), and pancreas (Norell et al., 1986; Risch, 2003).

Salted Foods

Case-control studies have found a positive association between stomach cancer risk with consumption of salted meat and fish (Boeing et al., 1991; Ward et al., 1999; Buiatti et al., 1989; Haenszel et al., 1972; Kono et al., 1988; Lee et al., 1995; Palli et al., 1992; Ramon et al., 1993); in addition, a cohort study found a two-fold increased risk of stomach cancer with salted fish consumption (Kneller et al., 1991). Salted meat and fish has also been associated with a 2.6-fold increased risk of colorectal cancer (Knekt et al., 1999). Some foods, such as salted fish, are preserved using nitrite salts and are thus a source of both salt and exogenous N-nitroso compounds (NOC) from the reaction between the nitrite and the secondary amines present in the fish. Chinese salted fish, for example, contains high levels of NOCs.

Nitrates/Nitrites And N-Nitroso Compounds (Nocs)

Meat may be associated with cancer risk by contributing to NOC exposure. NOCs are among the most powerful chemical carcinogens; therefore, even small amounts in the human body could be important. The carcinogenicity of NOCs has been tested in 39 different animal species, including six species of primate. Tumors have been induced in all species so far examined at a variety of sites and in a wide range of target cells. Thus, there is no reason to assume that humans are not susceptible to their actions.

There are two major routes of exposure to NOCs, by exogenous routes (from processed meats in particular) and by endogenous formation within the body, which is dose-dependently related to the amount of red meat in the diet. Exogenous exposure to NOCs occurs mainly by the inhalation or consumption of tobacco and preserved or heat-treated foods. Nitrite is added to processed meat as an antibacterial agent against Clostridium botulinum and as a cosmetic agent to react with myoglobin to produce the characteristic red-pink color of cured meats. Nitrate and nitrite are known precursors for NOC formation and, therefore, nitrite added to meat can form NOC in the meat. NOCs have also been detected in foods processed by smoking or direct fire-drying, which uses sufficient heat to oxidize molecular nitrogen to nitrogen oxides, which are able to nitrosate amines present in foods such as meat.

Dietary sources of nitrate and nitrite have not shown consistent associations with cancer risk. Some studies have found a positive association between foods high in nitrite, such as bacon and hot dogs, and esophageal cancer (Rogers et al., 1995), nasopharyngeal cancer (Ward et al., 2000), non-cardia gastric cancer (Mayne et al., 2001), pancreatic cancer (Coss et al., 2004), bladder cancer (Michaud et al., 2006), childhood leukemia, and brain cancer (Peters et al., 1994; Sarasua and Savitz, 1994; Kuijten et al., 1990); however, no association was found for colorectal (Knekt et al., 1999) or gastric cancer risk (Chyou et al., 1990; van Loon et al., 1997). Some studies have estimated overall NOC intake and have found significant positive associations with stomach cancer risk (Correa et al., 1985; Gonzalez et al., 1994; La Vecchia et al., 1995; Pobel et al., 1995), upper aerodigestive tract cancers (Rogers et al., 1995), and brain cancer (PrestonMartin, 1982). Childhood exposure to NOCs has been specifically associated with nasopharyngeal cancer (Ward et al., 2000). A study of esophageal cancer conducted in two different areas of China, a lowand a high-risk area, showed that NOC levels in the diet and daily excretion of NOC were significantly higher in the area at high risk for this cancer (Lin et al., 2002). The association between exogenous NOC exposure and cancer was directly investigated in 73 cases of colorectal cancer in a Finnish cohort of 9985 individuals (Knekt et al., 1999). This study investigated whether N-nitroso-dimethylamine (NDMA) intake or foods rich in N-nitrosamines are predictive for colorectal cancer. NDMA intake came from smoked and salted fish (52%) as well as cured meats and sausages (48%). This study found a significant two-fold increased risk of colorectal cancer in those with a high intake of NDMA (Knekt et al., 1999).

Endogenous NOC formation is thought to occur as a result of nitrosating agents, such as those derived from nitrite, reacting with nitrosatable substrates, the most commonly studied being secondary amines; this reaction can be catalyzed by nitrate reductase, which has an eightfold variation in activity among individuals. A study in rats harboring human fecal flora in their intestine and fed human diets showed a three-fold increase in bacterial nitrate reductase activity with a three-fold increase in meat consumption (Rumney et al., 1993).

Fecal NOC level is measured as apparent total N-nitroso compounds (ATNC), which is a proxy for endogenous N-nitrosation when exogenous NOC exposure is low. When nitrate is given to conventional and germ-free rats, ATNC remains low irrespective of the nitrate dose; however, in conventional rats, the level of nitrate in the water had a marked effect on the fecal ATNC levels (r ¼ 0.95, p < 0.01) (Massey et al., 1988). Furthermore, controlled human feeding studies have demonstrated a clear dose–response effect of red meat on fecal ATNC levels (Hughes et al., 2001). More recently, heme iron was identified as the component responsible for the enhancing effect of red meat on endogenous N-nitrosation (Bingham et al., 2002; Cross et al., 2003). A review of 33 studies considering the effect of iron on colorectal carcinogenesis, which weighted each study according to its design and number of subjects, revealed that the stronger studies did find a positive association between dietary iron or iron stores and colorectal cancer risk (Nelson, 2001). There are no epidemiologic studies assessing the effect of measured heme iron intake from different meats and cancer risk.

Meat Cooking Methods

According to the WCRF report, high-temperature cooking methods, such as pan-frying or grilling/barbecuing, are ‘possibly’ contributing to the risk of both stomach and colorectal cancers (World Cancer Research Fund, 1997). Case-control studies of colorectal adenoma (Gunter, 2005; Probst-Hensch, 1997; Sinha, 1999), colorectal cancer (Butler et al., 2003; Gerhardsson de Verdier et al., 1991; Peters et al., 1989; Wohlleb et al., 1990), and pancreatic cancer (Anderson et al., 2002; Ghadirian et al., 1995; Ji et al., 1995; Norell et al., 1986) have found elevated risks for high-temperature cooking methods. Frying/grilling has also been associated with increased risks of NHL (Chang et al., 2005) as well as pancreatic (Norell et al., 1986), lung (Sinha et al., 1998), and bladder cancer (Steineck et al., 1990). Furthermore, the degree to which the meat is cooked is also thought to affect risk of some cancers. Several case-control studies investigating the role of meat doneness level on the risk of colorectal adenoma (Probst-Hensch, 1997; Sinha et al., 1999) or colorectal cancer (Butler et al., 2003; Gerhardsson de Verdier et al., 1991; Lang et al., 1994; Nowell et al., 2002) have reported elevated risks for wellor very well-done meat consumption. Other studies have found similar associations for well-done meat intake and tumors of the stomach (Ward et al., 1997), prostate (Cross et al., 2005; Norrish et al., 1999), breast (Zheng et al., 1998), and lung (Sinha et al., 1998). However, other studies have not found any associations for high-temperature cooking methods or for well-done meat consumption and colorectal cancer (Augustsson et al., 1999; Kampman et al., 1999; Lyon and Mahoney, 1988; Muscat and Wynder, 1994), pancreatic cancer (Baghurst et al., 1991; Gold et al., 1985; Mack et al., 1986; Stolzenberg-Solomon et al., 2002), or NHL (Chiu et al., 1996; Cross et al., 2006; Chang et al., 2005; Zhang et al., 1999), for example. Relatively large risks are observed when a combination of method and doneness is considered; for example, fried meat with a heavily browned surface increased the risk of colon cancer by 2.8-fold and rectal cancer by six-fold in a Swedish casecontrol study (559 cases and 505 controls) (Gerhardsson de Verdier et al., 1991).

Cooking method and doneness are thought to be surrogates for mutagens formed in meat as a result of the cooking process. Laboratory results have shown that meats cooked at high temperatures contain heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) ( Jagerstad et al., 1991).

Heterocyclic Amines (HCAs)

The most abundant HCAs in cooked meat are PhIP (2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine) and MeIQx (2-amino-3,8-dimethylimidazo(4,5-f )quinoxaline) and, after a cooked meat meal, they are also the two HCAs that are most absorbed (Lynch et al., 1992). In 1993, the International Agency for Research on Cancer found that there was sufficient evidence from experimental animal studies to conclude that the HCAs IQ (2-amino- 3-methylimidazo(4,5-f )quinoline), MeIQ (2-amino-3,4dimethylimidazo(4,5-f )quinoline), MeIQx, DiMeIQx (2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline), and PhIP were carcinogenic (IARC, 1993). Over 20 individual HCAs have been identified, at least ten of which have been found to induce tumors in lab animals at multiple sites. PhIP specifically has been associated with an increased risk of intestinal and mammary adenocarcinomas in rodents, as well as prostate tumors in rats. MeIQx can induce tumors at multiple sites in rodents such as the liver and lung as well as lymphomas and leukemias. In addition, the DNA adducts and mutations from such HCA exposure show similarities between experimental animals and humans; these adducts have been detected in a wide variety of tissues and organs. A small pilot study in humans showed that colonic DNA adducts were formed in a dose-dependent manner after oral administration of a capsule containing MeIQx (Turteltaub et al., 1999). In addition, DNA and protein adducts were formed in the colon and blood, respectively, of humans receiving a dose of PhIP equivalent to the level found in 175 g of very well-done chicken, although the adducts were unstable and declined over 24 h (Dingley et al., 1999).

In more recent studies, questionnaires with detailed cooking and doneness information linked to a HCA database are used to estimate individual HCA intake. The HCA database was created by measuring levels of HCAs in a variety of meats, cooked by different methods to a range of doneness levels (rare, medium, well-done, and very well done) (Knize et al., 1995; Sinha et al., 1995; 1998a,b). Two case-control studies found a significant increased risk associated with HCAs; one found a 1.8-fold increased risk of colon cancer with DiMeIQx intake (Butler et al., 2003), and the other found 2.1to 2.5-fold increased risks for colorectal adenoma with DiMeIQx, MeIQx, and PhIP intake (Sinha et al., 2001). The findings for MeIQx were replicated in a case-control study (157 cases and 380 controls) of colorectal cancer, which showed a significant four-fold increased risk of colorectal cancer in the highest quartile of MeIQx intake (Nowell et al., 2002). One of the most recent studies to publish results on HCA intake and colorectal cancer risk was a population-based study of 620 cases and 1038 controls; this study found that DiMeIQx intake was associated with a 1.8-fold risk, but no associations for MeIQx or PhIP (Butler et al., 2003). Specific HCAs have been investigated in two studies of prostate cancer. The first was a case-control study of 317 cases that found no association (Norrish et al., 1999); the second was a cohort study with 1338 cases, and the authors found PhIP intake to significantly increase the risk for prostate cancer (Cross et al., 2005), which confirms animal findings that suggest PhIP is a prostate-specific carcinogen (Shirai et al., 1999). Furthermore, a case-control study of pancreatic cancer found MeIQx, DiMeIQx, and PhIP were all positively associated with risk (Anderson et al., 2005). However, other studies have shown no association between specific HCA intake and risk of NHL (Cross et al., 2006), colorectal adenoma (Gunter et al., 2005), colorectal cancer, or bladder cancer (Augustsson et al., 1999).

Polycyclic Aromatic Hydrocarbons (PAHs)

PAHs are mutagenic compounds formed in foods processed by smoking, such as meat, as well as in meat cooked by grilling/barbecuing. Meat cooked over a flame results in fat and meat juices dripping onto the hot fire, which yields flames containing a number of PAHs. These PAHs adhere to the surface of the food. Benzo[a]pyrene (B[a]P) is one of the most potent PAH carcinogens in animal studies and can induce leukemia as well as gastric, pulmonary, fore-stomach, esophageal, and tongue tumors in rodents (Culp et al., 1998). Grilled and well-done steak, hamburger, and chicken contain the highest levels of B[a]P, containing up to 4 ng of B[a]P per gram of cooked meat (Kazerouni et al., 2001). Dietary exposure to PAHs is thought to be important, since the intake of well-done meat is more correlated to blood PAH adducts than smoking (Rothman et al., 1990; 1993).

Epidemiologic studies investigating the association between dietary intake of PAHs and cancer have generally proven to be null for colon (Butler et al., 2003) and prostate cancer (Cross et al., 2005). However, case-control studies of colorectal adenoma (Gunter et al., 2005; Sinha et al., 2005) and pancreatic cancer (Anderson et al., 2005) found elevated risks for those in the top, versus bottom, quantile of intake.

Conclusions

Red meat continues to be implicated as a risk factor for carcinogenesis. However, there are limitations to the current literature. Much of the published literature has limited statistical power to examine the relationship of specific types of meat with cancer or within sub-sites. There is a lack of standardization in how meat items are defined, as well as heterogeneity in meat products throughout the globe. Currently, most epidemiologic studies rely on the food frequency questionnaire, which is associated with a degree of measurement error. Furthermore, many of the studies do not include detailed meat-specific components, including information on preparation, cooking methods, and doneness level, in their questionnaires.

Studies have clearly shown that red meat dosedependently increases the endogenous formation of NOCs. However, the carcinogenic potential of such an increase needs to be verified by the characterization of the precise NOC species being formed. Further research is also needed to elucidate the role of iron in cancer risk and to determine whether any such risks associated with iron are the result of a catalytic role in endogenous NOC formation.

It is likely that HCA and PAH intake, determined by meat cooking technique and doneness level, makes a small contribution to cancer risk. However, the normal intake of HCAs is many orders of magnitude below the exposure levels that induce cancer in animal models; the evidence for PAHs also is weaker. Nevertheless, one must consider species differences and the possibility that humans may be more susceptible to the action of these compounds than rodents.

In order to advance the field of meat-related mutagens, the methods of exposure assessment must be further improved. Detailed questionnaires must be used in conjunction with reliable biomarkers in large prospective studies to accurately investigate the associations between meat, meat cooking and preserving methods, and cancer risk.

Bibliography:

Anderson KE, Kadlubar FF, Kulldorff M, et al. (2005) Dietary intake of heterocyclic amines and benzo(a)pyrene: associations with pancreatic cancer. Cancer Epidemiology Biomarkers and Prevention 14(9): 2261–2265.
Anderson KE, Sinha R, Kulldorff M, et al. (2002) Meat intake and cooking techniques: associations with pancreatic cancer. Mutation Research 506– 507: 225–231.
Augustsson K, Skog K, Jagerstad M, Dickman PW, and Steineck G (1999) Dietary heterocyclic amines and cancer of the colon, rectum, bladder, and kidney: a population-based study. Lancet 353(9154): 703–707.
Baghurst PA, McMichael AJ, Slavotinek AH, Baghurst KI, Boyle P, and Walker AM (1991) A case-control study of diet and cancer of the pancreas. American Journal of Epidemiology 134(2): 167–179.
Bingham SA, Hughes R, and Cross AJ (2002) Effect of white versus red meat on endogenous N-nitrosation in the human colon and further evidence of a dose response. Journal of Nutrition 132(11 Suppl): 3522S–3525S.
Boeing H, Jedrychowski W, Wahrendorf J, Popiela T, TobiaszAdamczyk B, and Kulig A (1991) Dietary risk factors in intestinal and diffuse types of stomach cancer: a multicenter case-control study in Poland. Cancer Causes Control 2(4): 227–233.
Bosetti C, Micelotta S, Dal Maso L, et al. (2004) Food groups and risk of prostate cancer in Italy. International Journal of Cancer 110(3): 424–428.
Boyd NF, Stone J, Vogt KN, Connelly BS, Martin LJ, and Minkin S (2003) Dietary fat and breast cancer risk revisited: a meta-analysis of the published literature. British Journal of Cancer 89(9): 1672–1685.
Bueno de Mesquita HB, Maisonneuve P, Runia S, and Moerman CJ (1991) Intake of foods and nutrients and cancer of the exocrine pancreas: a population-based case-control study in The Netherlands. International Journal of Cancer 48(4): 540–549.
Buiatti E, Palli D, Decarli A, et al. (1989) A case-control study of gastric cancer and diet in Italy. International Journal of Cancer 44(4): 611–616.
Butler LM, Sinha R, Millikan RC, et al. (2003) Heterocyclic amines, meat intake, and association with colon cancer in a population-based study. American Journal of Epidemiology 157(5): 434–445.
Chang ET, Smedby KE, Zhang SM, et al. (2005) Dietary factors and risk of non-hodgkin lymphoma in men and women. Cancer Epidemiology Biomarkers and Prevention 14(2): 512–520.
Chen H, Ward MH, Graubard BI, et al. (2002) Dietary patterns and adenocarcinoma of the esophagus and distal stomach. American Journal of Clinical Nutrition 75(1): 137–144.
Chiu BC, Cerhan JR, Folsom AR, et al. (1996) Diet and risk of non-Hodgkin lymphoma in older women. Journal of the American Medical Association 275(17): 1315–1321.
Cho E, Chen WY, Hunter DJ, et al. (2006) Red meat intake and risk of breast cancer among premenopausal women. Archives of Internal Medicine 166(20): 2253–2259.
Chyou PH, Nomura AM, Hankin JH, and Stemmermann GN (1990) A case-cohort study of diet and stomach cancer. Cancer Research 50(23): 7501–7504.
Chyou PH, Nomura AM, and Stemmermann GN (1993) A prospective study of diet, smoking, and lower urinary tract cancer. Annals of Epidemiology 3(3): 211–216.
Committee on Medical Aspects of Food and Nutrition Policy (1998) Nutritional aspects of the development of cancer. Report of the Working Group on Diet and Cancer of the Committee on Medical Aspects of Food and Nutrition Policy. London: HMSO.
Correa P, Fontham E, Pickle LW, Chen V, Lin YP, and Haenszel W (1985) Dietary determinants of gastric cancer in south Louisiana inhabitants. Journal of the National Cancer Institute 75(4): 645–654.
Coss A, Cantor KP, Reif JS, Lynch CF, and Ward MH (2004) Pancreatic cancer and drinking water and dietary sources of nitrate and nitrite. American Journal of Epidemiology 159(7): 693–701.
Coughlin SS, Calle EE, Patel AV, and Thun MJ (2000) Predictors of pancreatic cancer mortality among a large cohort of United States adults. Cancer Causes Control 11(10): 915–923.
Cross AJ, Pollock JR, and Bingham SA (2003) Haem, not protein or inorganic iron, is responsible for endogenous intestinal N-nitrosation arising from red meat. Cancer Research 63(10): 2358–2360.
Cross AJ, Peters U, Kirsh VA, et al. (2005) A prospective study of meat and meat mutagens and prostate cancer risk. Cancer Research 65(24): 11779–11784.
Cross AJ, Ward MH, Schenk M, et al. (2006) Meat and meat-mutagen intake and risk of non-Hodgkin lymphoma: results from a NCI-SEER case-control study. Carcinogenesis 27(2): 293–297.
Culp SJ, Gaylor DW, Sheldon WG, Goldstein LS, and Beland FA (1998) A comparison of the tumors induced by coal tar and benzo[a]pyrene in a 2-year bioassay. Carcinogenesis 19(1): 117–124.
De Stefani E, Fierro L, Barrios E, and Ronco A (1998) Tobacco, alcohol, diet and risk of non-Hodgkin’s lymphoma: a case-control study in Uruguay. Leukaemia Research 22(5): 445–452.
Deneo-Pellegrini H, De Stefani E, Ronco A, and Mendilaharsu M (1999) Foods, nutrients and prostate cancer: a case-control study in Uruguay. British Journal of Cancer 80(3–4): 591–597.
Dingley KH, Curtis KD, Nowell S, Felton JS, Lang NP, and Turteltaub KW (1999) DNA and protein adduct formation in the colon and blood of humans after exposure to a dietary-relevant dose of 2-amino-1methyl-6-phenylimidazo[4,5-b]pyridine. Cancer Epidemiology Biomarkers and Prevention 8(6): 507–512.
Falk RT, Pickle LW, Fontham ET, Correa P, and Fraumeni JF Jr (1988) Life-style risk factors for pancreatic cancer in Louisiana: a case-control study. American Journal of Epidemiology 128(2): 324–336.
Farrow DC and Davis S (1990) Diet and the risk of pancreatic cancer in men. American Journal of Epidemiology 132(3): 423–431.
Fernandez E, La Vecchia C, and Decarli A (1996) Attributable risks for pancreatic cancer in northern Italy. Cancer Epidemiology Biomarkers and Prevention 5(1): 23–27.
Franceschi S, Serraino D, Carbone A, Talamini R, and La Vecchia C (1989) Dietary factors and non-Hodgkin’s lymphoma: a casecontrol study in the northeastern part of Italy. Nutrition and Cancer 12(4): 333–341.
Galanis DJ, Kolonel LN, Lee J, and Nomura A (1998) Intakes of selected foods and beverages and the incidence of gastric cancer among the Japanese residents of Hawaii: a prospective study. International Journal of Epidemiology 27(2): 173–180.
Gann PH, Hennekens CH, Sacks FM, Grodstein F, Giovannucci EL, and Stampfer MJ (1994) Prospective study of plasma fatty acids and risk of prostate cancer. Journal of the National Cancer Institute 86(4): 281–286.
Gerhardsson de Verdier M, Hagman U, Peters RK, Steineck G, and Overvik E (1991) Meat, cooking methods and colorectal cancer: a case-referent study in Stockholm. International Journal of Cancer 49(4): 520–525.
Ghadirian P, Baillargeon J, Simard A, and Perret C (1995) Food habits and pancreatic cancer: a case-control study of the Francophone community in Montreal, Canada. Cancer Epidemiology Biomarkers and Prevention 4(8): 895–899.
Giovannucci E, Rimm EB, Colditz GA, et al. (1993) A prospective study of dietary fat and risk of prostate cancer. Journal of the National Cancer Institute 85(19): 1571–1579.
Gold EB, Gordis L, Diener MD, et al. (1985) Diet and other risk factors for cancer of the pancreas. Cancer 55(2): 460–467.
Gonzalez CA, Riboli E, Badosa J, et al. (1994) Nutritional factors and gastric cancer in Spain. American Journal of Epidemiology 139(5): 466–473.
Gonzalez CA, Sanz JM, Marcos G, et al. (1991) Dietary factors and stomach cancer in Spain: a multi-centre case-control study. International Journal of Cancer 49(4): 513–519.
Gonzalez CA, Jakszyn P, Pera G, et al. (2006) Meat intake and risk of stomach and esophageal adenocarcinoma within the European Prospective Investigation Into Cancer and Nutrition (EPIC). Journal of the National Cancer Institute 98(5): 345–354.
Gronberg H, Damber L, and Damber JE (1996) Total food consumption and body mass index in relation to prostate cancer risk: a case-control study in Sweden with prospectively collected exposure data. Journal of Urology 155(3): 969–974.
Gunter MJ, Probst-Hensch NM, Cortessis VK, Kulldorff M, Haile RW, and Sinha R (2005) Meat intake, cooking-related mutagens and risk of colorectal adenoma in a sigmoidoscopy-based case-control study. Carcinogenesis 26(3): 637–642.
Haenszel W, Kurihara M, Segi M, and Lee RK (1972) Stomach cancer among Japanese in Hawaii. Journal of the National Cancer Institute 49(4): 969–988.
Hayes RB, Ziegler RG, Gridley G, et al. (1999) Dietary factors and risks for prostate cancer among blacks and whites in the United States. Cancer Epidemiology Biomarkers and Prevention 8(1): 25–34.
Hirayama T (1989) Epidemiology of pancreatic cancer in Japan. Japan Journal of Clinical Oncology 19(3): 208–215.
Hirayama T (1979) Epidemiology of prostate cancer with special reference to the role of diet. National Cancer Institute Monograph 53: 149–155.
Hoshiyama Y and Sasaba T (1992) A case-control study of stomach cancer and its relation to diet, cigarettes, and alcohol consumption in Saitama Prefecture, Japan. Cancer Causes Control 3(5): 441–448.
Hsing AW, McLaughlin JK, Schuman LM, et al. (1990) Diet, tobacco use, and fatal prostate cancer: results from the Lutheran Brotherhood Cohort Study. Cancer Research 50(21): 6836–6840.
Hughes R, Cross AJ, Pollock JR, and Bingham S (2001) Dosedependent effect of dietary meat on endogenous colonic N-nitrosation. Carcinogenesis 22(1): 199–202.
IARC (1993) IARC working group on the evaluation of carcingenic risks to humans: occupational exposures of hairdressers and barbers and personal use of hair colourants; some hair dyes, cosmetic colourants, industrial dyestuffs and aromatic amines. Lyon: France, IARC.
Isaksson B, Jonsson F, Pedersen NL, Larsson J, Feychting M, and Permert J (2002) Lifestyle factors and pancreatic cancer risk: a cohort study from the Swedish Twin Registry. International Journal of Cancer 98(3): 480–482.
Ito LS, Inoue M, Tajima K, et al. (2003) Dietary factors and the risk of gastric cancer among Japanese women: A comparison between the differentiated and non-differentiated subtypes. Annals of Epidemiology 13(1): 24–31.
Jagerstad M, Skog K, Grivas S, and Olsson K (1991) Formation of heterocyclic amines using model systems. Mutation Research 259 (3–4): 219–233.
Ji BT, Chow WH, Yang G, et al. (1998) Dietary habits and stomach cancer in Shanghai, China. International Journal of Cancer 76(5): 659–664.
Ji BT, Chow WH, Gridley G, et al. (1995) Dietary factors and the risk of pancreatic cancer: a case-control study in Shanghai China. Cancer Epidemiology Biomarkers and Prevention 4(8): 885–893.
Kampman E, Slattery ML, Bigler J, et al. (1999) Meat consumption, genetic susceptibility, and colon cancer risk: a United States multicenter case-control study. Cancer Epidemiology Biomarkers and Prevention 8(1): 15–24.
Kazerouni N, Sinha R, Hsu CH, Greenberg A, and Rothman N (2001) Analysis of 200 food items for benzo[a]pyrene and estimation of its intake in an epidemiologic study. Food and Chemical Toxicology 39(5): 423–436.
Key TJ, Fraser GE, Thorogood M, et al. (1999) Mortality in vegetarians and nonvegetarians: Detailed findings from a collaborative analysis of 5 prospective studies. American Journal of Clinical Nutrition 70(supplement 3): 516S–524S.
Knekt P, Jarvinen R, Dich J, and Hakulinen T (1999) Risk of colorectal and other gastro-intestinal cancers after exposure to nitrate, nitrite and N-nitroso compounds: a follow-up study. International Journal of Cancer 80(6): 852–856.
Kneller RW, McLaughlin JK, Bjelke E, et al. (1991) A cohort study of stomach cancer in a high-risk American population. Cancer 68(3): 672–678.
Knize MG, Dolbeare FA, Cunningham PL, and Felton JS (1995) Mutagenic activity and heterocyclic amine content of the human diet. Princess Takamatsu Symposia 23: 30–38.
Kono S, Ikeda M, Tokudome S, and Kuratsune M (1988) A case-control study of gastric cancer and diet in northern Kyushu, Japan. Japan Journal of Cancer Research 79(10): 1067–1074.
Kuijten RR, Bunin GR, Nass CC, and Meadows AT (1990) Gestational and familial risk factors for childhood astrocytoma: results of a casecontrol study. Cancer Research 50(9): 2608–2612.
La Vecchia C, D’Avanzo B, Airoldi L, Braga C, and Decarli A (1995) Nitrosamine intake and gastric cancer risk. European Journal of Cancer Prevention 4(6): 469–474.
La Vecchia C, Negri E, D’Avanzo B, et al. (1990) Medical history, diet and pancreatic cancer. Oncology 47(6): 463–466.
La Vecchia C and Negri E (1996) Nutrition and bladder cancer. Cancer Causes Control 7(1): 95–100.
Lang NP, Butler MA, Massengill J, et al. (1994) Rapid metabolic phenotypes for acetyltransferase and cytochrome P4501A2 and putative exposure to food-borne heterocyclic amines increase the risk for colorectal cancer or polyps. Cancer Epidemiology Biomarkers and Prevention 3(8): 675–682.
Larsson SC, Hakanson N, Permert J, and Wolk A (2006) Meat, fish, poultry and egg consumption in relation to risk of pancreatic cancer: a prospective study. International Journal of Cancer 118(11): 2866–2870.
Larsson SC and Wolk A (2006) Meat consumption and risk of colorectal cancer: A meta-analysis of prospective studies. International Journal of Cancer 119(11): 2657–2664.
Le Marchand L, Kolonel LN, Wilkens LR, Myers BC, and Hirohata T (1994) Animal fat consumption and prostate cancer: a prospective study in Hawaii. Epidemiology 5(3): 276–282.
Lee JK, Park BJ, Yoo KY, and Ahn YO (1995) Dietary factors and stomach cancer: a case-control study in Korea. International Journal of Epidemiology 24(1): 33–41.
Levi F, Pasche C, Lucchini F, Bosetti C, and La Vecchia C (2004) Processed meat and the risk of selected digestive tract and laryngeal neoplasms in Switzerland. Annuals of Oncology 15(2): 346–349.
Lin K, Shen W, Shen Z, Wu Y, and Lu S (2002) Dietary exposure and urinary excretion of total N-nitroso compounds, nitrosamino acids and volatile nitrosamine in inhabitants of highand low-risk areas for esophageal cancer in southern China. International Journal of Cancer 102(3): 207–211.
Lynch AM, Knize MG, Boobis AR, Gooderham NJ, Davies DS, and Murray S (1992) Intraand interindividual variability in systemic exposure in humans to 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, carcinogens present in cooked beef. Cancer Research 52(22): 6216–6223.
Lyon JL and Mahoney AW (1988) Fried foods and the risk of colon cancer. American Journal of Epidemiology 128(5): 1000–1006.
Lyon JL, Slattery ML, Mahoney AW, and Robison LM (1993) Dietary intake as a risk factor for cancer of the exocrine pancreas. Cancer Epidemiology Biomarkers and Prevention 2(6): 513–518.
Mack TM, Yu MC, Hanisch R, and Henderson BE (1986) Pancreas cancer and smoking, beverage consumption, and past medical history. Journal of the National Cancer Institute 76(1): 49–60.
Massey RC, Key PE, Mallett AK, and Rowland IR (1988) An investigation of the endogenous formation of apparent total N-nitroso compounds in conventional microflora and germ-free rats. Food and Chemical Toxicology 26(7): 595–600.
Mathew A, Gangadharan P, Varghese C, and Nair MK (2000) Diet and stomach cancer: a case-control study in South India. European Journal of Cancer Prevention 9(2): 89–97.
Mayne ST, Risch HA, Dubrow R, et al. (2001) Nutrient intake and risk of subtypes of esophageal and gastric cancer. Cancer Epidemiology Biomarkers and Prevention 10(10): 1055–1062.
McCullough ML, Robertson AS, Jacobs EJ, Chao A, Calle EE, and Thun MJ (2001) A prospective study of diet and stomach cancer mortality in United States men and women. Cancer Epidemiology Biomarkers and Prevention 10(11): 1201–1205.
Michaud DS, Giovannucci E, Willett WC, Colditz GA, and Fuchs CS (2003) Dietary meat, dairy products, fat, and cholesterol and pancreatic cancer risk in a prospective study. American Journal of Epidemiology 157(12): 1115–1125.
Michaud DS, Augustsson K, Rimm EB, Stampfer MJ, Willet WC, and Giovannucci E (2001) A prospective study on intake of animal products and risk of prostate cancer. Cancer Causes Control 12(6): 557–567.
Michaud DS, Holick CN, Giovannucci E, and Stampfer MJ (2006) Meat intake and bladder cancer risk in 2 prospective cohort studies. American Journal of Clinical Nutrition 84(5): 1177–1183.
Mills PK, Beeson WL, Abbey DE, Fraser GE, and Phillips RL (1988) Dietary habits and past medical history as related to fatal pancreas cancer risk among Adventists. Cancer 61(12): 2578–2585.
Mills PK, Beeson WL, Phillips RL, and Fraser GE (1991) Bladder cancer in a low risk population: results from the Adventist Health Study. American Journal of Epidemiology 133(3): 230–239.
Missmer SA, Smith-Warner SA, Spiegelman D, et al. (2002) Meat and dairy food consumption and breast cancer: a pooled analysis of cohort studies. International Journal of Epidemiology 31(1): 78–85.
Mizuno S, Watanabe S, Nakamura K, et al. (1992) A multi-institute case- control study on the risk factors of developing pancreatic cancer. Japan Journal of Clinical Oncology 22(4): 286–291.
Muscat JE and Wynder EL (1994) The consumption of well-done red meat and the risk of colorectal cancer. American Journal of Public Health 84(5): 856–858.
Nelson RL (2001) Iron and colorectal cancer risk: human studies. Nutrition Review 59(5): 140–148.
Ngoan LT, Mizoue T, Fujino Y, Tokui N, and Yoshimura T (2002) Dietary factors and stomach cancer mortality. British Journal of Cancer 87(1): 37–42.
Nomura A, Grove JS, Stemmermann GN, and Severson RK (1990) A prospective study of stomach cancer and its relation to diet, cigarettes, and alcohol consumption. Cancer Research 50(3): 627–631.
Norat T, Lukanova A, Ferrari P, and Riboli E (2002) Meat consumption and colorectal cancer risk: Dose-response meta-analysis of epidemiological studies. International Journal of Cancer 98(2): 241–256.
Norell SE, Ahlbom A, Erwald R, et al. (1986) Diet and pancreatic cancer: a case-control study. American Journal of Epidemiology 124(6): 894–902.
Norrish AE, Ferguson LR, Knize MG, Felton JS, Sharpe SJ, and Jackson RT (1999) Heterocyclic amine content of cooked meat and risk of prostate cancer. Journal of the National Cancer Institute 91(23): 2038–2044.
Nothlings U, Wilkens LR, Murphy SP, Hankin JH, Henderson BE, and Kolonel LN (2005) Meat and fat intake as risk factors for pancreatic cancer: the multiethnic cohort study. Journal of the National Cancer Institute 97(19): 1458–1465.
Nowell S, Coles B, Sinha R, et al. (2002) Analysis of total meat intake and exposure to individual heterocyclic amines in a case-control study of colorectal cancer: contribution of metabolic variation to risk. Mutation Research 506–507: 175–185.
Olsen GW, Mandel JS, Gibson RW, Wattenberg LW, and Schuman LM (1989) A case-control study of pancreatic cancer and cigarettes, alcohol, coffee and diet. American Journal of Public Health 79(8): 1016–1019.
Palli D, Bianchi S, Decarli A, et al. (1992) A case-control study of cancers of the gastric cardia in Italy. British Journal of Cancer 65(2): 263–266.
Peters RK, Garabrant DH, Yu MC, and Mack TM (1989) A case-control study of occupational and dietary factors in colorectal cancer in young men by subsite. Cancer Research 49(19): 5459–5468.
Peters JM, Preston-Martin S, London SJ, Bowman JD, Buckley JD, and Thomas DC (1994) Processed meats and risk of childhood leukemia (California, USA). Cancer Causes Control 5(2): 195–202.
Pobel D, Riboli E, Cornee J, Hemon B, and Guyader M (1995) Nitrosamine, nitrate and nitrite in relation to gastric cancer: a casecontrol study in Marseille, France. European Journal of Epidemiology 11(1): 67–73.
Preston-Martin S, Yu MC, Benton B, and Henderson BE (1982) N-Nitroso compounds and childhood brain tumors: a case-control study. Cancer Research 42(12): 5240–5245.
Probst-Hensch NM, Sinha R, Longnecker MP, et al. (1997) Meat preparation and colorectal adenomas in a large sigmoidoscopy-based case-control study in California (United States). Cancer Causes Control 8(2): 175–183.
Purdue MP, Bassani DG, Klar NS, Sloan M, and Kreiger N (2004) Dietary factors and risk of non-Hodgkin lymphoma by histologic subtype: a case-control analysis. Cancer Epidemiology Biomarkers and Prevention 13(10): 1665–1676.
Rajkumar T, Sridhar H, Balaram P, et al. (2003) Oral cancer in Southern India: the influence of body size, diet, infections and sexual practices. European Journal of Cancer Prevention 12(2): 135–143.
Ramon JM, Serra L, Cerdo C, and Oromi J (1993) Dietary factors and gastric cancer risk. A case-control study in Spain. Cancer 71(5): 1731–1735.
Raymond L, Infante F, Tuyns AJ, Voirol M, and Lowenfels AB (1987) [Diet and cancer of the pancreas]. Gastroenterologie Clinique et Biologique 11(6–7): 488–492.
Risch HA, Jain M, Choi NW, et al. (1985) Dietary factors and the incidence of cancer of the stomach. American Journal of Epidemiology 122(6): 947–959.
Risch HA (2003) Etiology of pancreatic cancer, with a hypothesis concerning the role of N-nitroso compounds and excess gastric acidity. Journal of the National Cancer Institute 95(13): 948–960.
Rodriguez C, McCullough ML, Mondul AM, et al. (2006) Meat consumption among Black and White men and risk of prostate cancer in the Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiology Biomarkers and Prevention 15(2): 211–216.
Rogers MA, Vaughan TL, Davis S, and Thomas DB (1995) Consumption of nitrate, nitrite, and nitrosodimethylamine and the risk of upper aerodigestive tract cancer. Cancer Epidemiology Biomarkers and Prevention 4(1): 29–36.
Rothman N, Correa-Villasenor A, Ford DP, et al. (1993) Contribution of occupation and diet to white blood cell polycyclic aromatic hydrocarbon-DNA adducts in wildland firefighters. Cancer Epidemiology Biomarkers and Prevention 2(4): 341–347.
Rothman N, Poirier MC, Baser ME, et al. (1990) Formation of polycyclic aromatic hydrocarbon-DNA adducts in peripheral white blood cells during consumption of charcoal-broiled beef. Carcinogenesis 11(7): 1241–1243.
Rumney CJ, Rowland IR, Coutts TM, et al. (1993) Effects of risk-associated human dietary macrocomponents on processes related to carcinogenesis in human-flora-associated (HFA) rats. Carcinogenesis 14(1): 79–84.
Sandhu MS, White IR, and McPherson K (2001) Systematic review of the prospective cohort studies on meat consumption and colorectal cancer risk: A meta-analytical approach. Cancer Epidemiology Biomarkers and Prevention 10(5): 439–446.
Sarasua S and Savitz DA (1994) Cured and broiled meat consumption in relation to childhood cancer: Denver, Colorado (United States). Cancer Causes Control 5(2): 141–148.
Schuurman AG, van den Brandt PA, Dorant E, and Goldbohm RA (1999) Animal products, calcium and protein and prostate cancer risk in The Netherlands Cohort Study. British Journal of Cancer 80(7): 1107–1113.
Shirai T, Cui L, Takahashi S, et al. (1999) Carcinogenicity of 2-amino-1methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) in the rat prostate and induction of invasive carcinomas by subsequent treatment with testosterone propionate. Cancer Letters 143(2): 217–221.
Silverman DT, Swanson CA, Gridley G, et al. (1998) Dietary and nutritional factors and pancreatic cancer: a case-control study based on direct interviews. Journal of the National Cancer Institute 90(22): 1710–1719.
Sinha R, Chow WH, Kulldorff M, et al. (1999) Well-done, grilled red meat increases the risk of colorectal adenomas. Cancer Research 59(17): 4320–4324.
Sinha R, Kulldorff M, Curtin J, Brown CC, Alavanja MC, and Swanson CA (1998) Fried, well-done red meat and risk of lung cancer in women (United States). Cancer Causes Control 9(6): 621–630.
Sinha R, Knize MG, Salmon CP, et al. (1998) Heterocyclic amine content of pork products cooked by different methods and to varying degrees of doneness. Food and Chemical Toxicology 36(4): 289–297.
Sinha R, Rothman N, Brown ED, et al. (1995) High concentrations of the carcinogen 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) occur in chicken but are dependent on the cooking method. Cancer Research 55(20): 4516–4519.
Sinha R, Rothman N, Salmon CP, et al. (1998) Heterocyclic amine content in beef cooked by different methods to varying degrees of doneness and gravy made from meat drippings. Food and Chemical Toxicology 36(4): 279–287.
Sinha R, Kulldorff M, Chow WH, Denobile J, and Rothman N (2001) Dietary intake of heterocyclic amines, meat-derived mutagenic activity, and risk of colorectal adenomas. Cancer Epidemiology Biomarkers and Prevention 10(5): 559–562.
Sinha R, Kulldorff M, Gunter MJ, Strickland P, and Rothman N (2005) Dietary benzo[a]pyrene intake and risk of colorectal adenoma. Cancer Epidemiology Biomarkers and Prevention 14(8): 2030–2034.
Soler M, Chatenoud L, La Vecchia C, Franceschi S, and Negri E (1998) Diet, alcohol, coffee and pancreatic cancer: final results from an Italian study. European Journal of Cancer 7(6): 455–460.
Steineck G, Hagman U, Gerhardsson M, and Norell SE (1990) Vitamin A supplements, fried foods, fat and urothelial cancer. A case-referent study in Stockholm in 1985–87. International Journal of Cancer 45(6): 1006–1011.
Steineck G, Norell SE, and Feychting M (1988) Diet, tobacco and urothelial cancer. A 14-year follow-up of 16,477 subjects. Acta Oncologica 27(4): 323–327.
Steinmaus CM, Nunez S, and Smith AH (2000) Diet and bladder cancer: a meta-analysis of six dietary variables. American Journal of Epidemiology 151(7): 693–702.
Stolzenberg-Solomon RZ, Pietinen P, Taylor PR, Virtamo J, and Albanes D (2002) Prospective study of diet and pancreatic cancer in male smokers. American Journal of Epidemiology 155(9): 783–792.
Talamini R, Polesel J, Montella M, et al. (2006) Food groups and risk of non-Hodgkin lymphoma: a multicenter, case-control study in Italy. International Journal of Cancer 118(11): 2871–2876.
Tavani A, La Vecchia C, Gallus S, et al. (2000) Red meat intake and cancer risk: a study in Italy. International Journal of Cancer 86(3): 425–428.
Tavani A, Pregnolato A, Negri E, et al. (1997) Diet and risk of lymphoid neoplasms and soft tissue sarcomas. Nutrition and Cancer 27(3): 256–260.
Taylor EF, Burley VJ, Greenwood DC, and Cade JE (2007) Meat consumption and risk of breast cancer in the UK Women’s Cohort Study. British Journal of Cancer 96(7): 1139–1146.
Turteltaub KW, Dingley KH, Curtis KD, et al. (1999) Macromolecular adduct formation and metabolism of heterocyclic amines in humans and rodents at low doses. Cancer Letters 143(2): 149–155.
van den Brandt PA, Botterweck AA, and Goldbohm RA (2003) Salt intake, cured meat consumption, refrigerator use and stomach cancer incidence: a prospective cohort study (Netherlands). Cancer Causes Control 14(5): 427–438.
van Loon AJ, Botterweck AA, Goldbohm RA, Brants HA, and van den Brandt PA (1997) Nitrate intake and gastric cancer risk: results from the Netherlands cohort study. Cancer Letters 114(1–2): 259–261.
Veierod MB, Laake P, and Thelle DS (1997) Dietary fat intake and risk of prostate cancer: a prospective study of 25 708 Norwegian men. International Journal of Cancer 73(5): 634–638.
Villeneuve PJ, Johnson KC, Kreiger N, and Mao Y (1999) Risk factors for prostate cancer: results from the Canadian National Enhanced Cancer Surveillance System. The Canadian Cancer Registries Epidemiology Research Group. Cancer Causes Control 10(5): 355–367.
Ward MH, Pan WH, Cheng YJ, et al. (2000) Dietary exposure to nitrite and nitrosamines and risk of nasopharyngeal carcinoma in Taiwan. International Journal of Cancer 86(5): 603–609.
Ward MH and Lopez-Carrillo L (1999) Dietary factors and the risk of gastric cancer in Mexico City. American Journal of Epidemiology 149(10): 925–932.
Ward MH, Sinha R, Heineman EF, et al. (1997) Risk of adenocarcinoma of the stomach and esophagus with meat cooking method and doneness preference. International Journal of Cancer 71(1): 14–19.
Ward MH, Zahm SH, Weisenburger DD, et al. (1994) Dietary factors and non-Hodgkin’s lymphoma in Nebraska (United States). Cancer Causes Control 5(5): 422–432.
Whittemore AS, Kolonel LN, Wu AH, et al. (1995) Prostate cancer in relation to diet, physical activity, and body size in blacks, whites, and Asians in the United States and Canada. Journal of the National Cancer Institute 87(9): 652–661.
Wilkens LR, Kadir MM, Kolonel LN, Nomura AM, and Hankin JH (1996) Risk factors for lower urinary tract cancer: the role of total fluid consumption, nitrites and nitrosamines, and selected foods. Cancer Epidemiology Biomarkers and Prevention 5(3): 161–166.
Wohlleb JC, Hunter CF, Blass B, Kadlubar FF, Chu DZ, and Lang NP (1990) Aromatic amine acetyltransferase as a marker for colorectal cancer: environmental and demographic associations. International Journal of Cancer 46(1): 22–30.
World Cancer Research Fund (1997) Food, Nutrition and Cancer: A Global Perspective. Washington, DC: World Cancer Research Fund.
Zhang ZF, Kurtz RC, Yu GP, et al. (1997) Adenocarcinomas of the esophagus and gastric cardia: the role of diet. Nutrition and Cancer 27(3): 298–309.
Zhang S, Hunter DJ, Rosner BA, et al. (1999) Dietary fat and protein in relation to risk of non-Hodgkin’s lymphoma among women. Journal of the National Cancer Institute 91(20): 1751–1758.
Zheng W, Gustafson DR, Sinha R, et al. (1998) Well-done meat intake and the risk of breast cancer. Journal of the National Cancer Institute 90(22): 1724–1729.
Zheng W, McLaughlin JK, Gridley G, et al. (1993) A cohort study of smoking, alcohol consumption, and dietary factors for pancreatic cancer (United States). Cancer Causes Control 4(5): 477–482.
Zheng T, Holford TR, Leaderer B, et al. (2004) Diet and nutrient intakes and risk of Non-Hodgkin’s lymphoma in connecticut women. American Journal of Epidemiology 159(5): 454–466.